title: Prospective investigations of concentration-clinical response for immunosuppressive drugs provide the scientific basis for therapeutic drug monitoring.
abstract: The performance of prospective concentration-clinical response investigations during the early stages of the development of new therapeutic agents can provide a more rigorous basis for therapeutic drug monitoring than the traditional retrospective review of drug concentrations vs clinical outcome. Here we discuss the application of the multicenter randomized concentration-controlled clinical trial study design, and related study designs, as applied to older commonly used and monitored drugs and to two new immunosuppressant drugs, mycophenolate mofetil and tacrolimus. Such studies can provide a more rigorous basis for assessing the risk/benefit associated with a target drug concentration in the individual patient and for designing future prospective pharmacokinetic and therapeutic drug monitoring investigations.
authors.affiliation: Department of Pathology & Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia 19104, USA. shawlmj@mail.med.upenn.edu
authors.forename: L M
authors.initials: LM
authors.lastname: Shaw
authors.forename: B
authors.initials: B
authors.lastname: Kaplan
authors.forename: K L
authors.initials: KL
authors.lastname: Brayman
mesh_terms: D002986:Clinical Trials as Topic; D016572:Cyclosporine / Q000097:blood / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000032:analysis*; D016030:Kidney Transplantation; D008094:Lithium / Q000097:blood; D016031:Liver Transplantation; D009173:Mycophenolic Acid / Q000097:blood; D004364:Pharmaceutical Preparations / Q000032:analysis; D016559:Tacrolimus / Q000097:blood / Q000633:toxicity
chemical_list: D007166:Immunosuppressive Agents; D004364:Pharmaceutical Preparations; D016572:Cyclosporine; D008094:Lithium; D009173:Mycophenolic Acid; D016559:Tacrolimus